ABSTRACT The Assays & Cell Models Core (Core B) provides resources for in vitro testing of CF drug candidates identified by high-throughput screening (Core A). Core B performs electrophysiological and optical assays of ion channel and transporter activity, and epithelial cell function, in CF-relevant cell models. The assays use immortalized cell models and primary airway cell cultures from human sources that are generated and provided by the Core. In addition, Core B generates new cell lines to enable screening assays. The assays supported by Core B are critical to the advancement of projects on both pulmonary and non-pulmonary CF diseases manifestations. Core B interfaces directly with all other Cores in the Center, for instance by testing focused analog libraries generated by the Chemistry Core (Core C) in order to prioritize compounds for testing in rodent models (Core D). The most heavily used assay in Core B is measurement of short-circuit current. Other major Core B assays include optical measurements of CF-relevant airway properties, including airway surface liquid (ASL) volume and ionic content (pH, [Cl-], [Na+]). The resources supported by Core B are also available to advance basic and translational research projects on CF pathophysiology at UCSF. Of the 23 projects in the research base, it is anticipated that at least 15 will use Core B resources. The reimagined Assays & Cell Models Core will continue to meet ongoing workloads and adapt to requirements of new projects and research directions.